Targeted immunotolerance

Abstract

Methods and compounds for conferring site-specific or local immune privilege.

What is claimed is: 
     
       1. A therapeutic compound having the formula from N-terminus to C-terminus:
 Chain 1: [VH1-CH1]-[CH2-CH3]-Linker A-scFv; 
 Chain 2: [VH1-CH1]-[CH2-CH3]-Linker A-scFv; 
 Chain 3: [VL1-CL]; and 
 Chain 4: [VL1-CL]; 
 wherein chains 1 and 2 are identical to each other, and chains 3 and 4 are identical to each other; 
 wherein chain 1 forms a homodimer with chain 2, and chain 3 and 4 associate with each VH1-CH1 domain of chain 1 and chain 2 to form two functional Fab units; 
 wherein CH2-CH3 comprises the Fc region; 
 wherein each Fab unit is an anti-PD-1 agonist antibody and each scFv unit is a scFv that binds to MAdCAM; 
 wherein each scFv unit has the formula of 5′-VL2-Linker B-VH2-3′, or 5′-VH2-Linker B-VL2-3′ 
 wherein Linker A and Linker B are each, independently, a peptide linker. 
 
     
     
       2. A nucleic acid encoding a therapeutic compound of  claim 1 . 
     
     
       3. The therapeutic compound of  claim 1 , wherein the Fab unit is a Fab or scFab. 
     
     
       4. The therapeutic compound of  claim 1 , wherein the peptide linker comprises glycine, serine, or alanine amino acid residues. 
     
     
       5. The therapeutic compound of  claim 1 , wherein the peptide linker is a glycine/serine linker. 
     
     
       6. A therapeutic compound comprising a polypeptide, wherein the polypeptide consists of a polypeptide having the formula from N-terminus to C-terminus:
 Chain 1: [VH1-CH1]-[CH2-CH3]-Linker A-scFv 
 Chain 2: [VH1-CH1]-[CH2-CH3]-Linker A-scFv 
 Chain 3: [VL1-CL] 
 Chain 4: [VL1-CL]; 
 wherein chains 1 and 2 are identical to each other, and chains 3 and 4 are identical to each other; 
 wherein chain 1 forms a homodimer with chain 2, and chain 3 and 4 associate with each VH1-CH1 domain of chain 1 and chain 2 to form two functional Fab units; 
 wherein CH2-CH3 comprises the Fc region; 
 wherein each Fab unit is an anti-PD-1 agonist each scFv unit is a scFv that binds to MAdCAM; 
 wherein each scFv unit has the formula of 5′-VL2-Linker B-VH2-3′, or 5′-VH2-Linker B-VL2-3′ 
 
       wherein Linker A and Linker B are each, independently, a peptide linker. 
     
     
       7. A composition comprising a single active therapeutic compound, wherein the single active therapeutic compound is the therapeutic compound of  claim 1 .